Xinyang Tablets ameliorate ventricular remodeling in heart failure via FTO/m6A signaling pathway.
10.19540/j.cnki.cjcmm.20241107.702
- Author:
Dong-Hua LIU
1
;
Zi-Ru LI
1
;
Si-Jing LI
1
;
Xing-Ling HE
1
;
Xiao-Jiao ZHANG
1
;
Shi-Hao NI
2
;
Wen-Jie LONG
3
;
Hui-Li LIAO
3
;
Zhong-Qi YANG
4
;
Xiao-Ming DONG
3
Author Information
1. State Key Laboratory of Traditional Chinese Medicine Syndrome, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China the First School of Clinical Medicine, Guangzhou University of Chinese Medicine Guangzhou 510407, China Lingnan Medical Research Center, Guangzhou University of Chinese Medicine Guangzhou 510405, China.
2. State Key Laboratory of Traditional Chinese Medicine Syndrome, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Lingnan Medical Research Center, Guangzhou University of Chinese Medicine Guangzhou 510405, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
3. Department of Geriatrics, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
4. State Key Laboratory of Traditional Chinese Medicine Syndrome, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Department of Geriatrics, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
- Publication Type:Journal Article
- Keywords:
FTO/m6A;
Xinyang Tablets;
heart failure;
ventricular remodeling
- MeSH:
Animals;
Ventricular Remodeling/drug effects*;
Heart Failure/physiopathology*;
Signal Transduction/drug effects*;
Mice;
Male;
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics*;
Drugs, Chinese Herbal/administration & dosage*;
Mice, Inbred C57BL;
Humans;
Adenosine/analogs & derivatives*;
Myocytes, Cardiac/metabolism*;
Disease Models, Animal
- From:
China Journal of Chinese Materia Medica
2025;50(4):1075-1086
- CountryChina
- Language:Chinese
-
Abstract:
The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
